Inherent in the approach to phase-appropriate development is the need for multiple process development cycles. A major advantage in this approach is that resources can be minimized in the development of early phase programs, which can be then put toward later phase programs that have a higher probability for commercial success. In this paradigm, it is the goal for early development to quickly transition from research to the clinic with clinical timelines being the main development constraint. Subsequently, the goal of late stage development is the generation of a commercially viable process with matching early-phase product quality being the main development constraint. The length of clinical timelines can have additional impact on how development cycles are assessed and initiated where short timelines pressure early phase processes to deliver commercial ready processes and long timelines push late phase processes to higher titers. During late-stage development, media components are often screened and balanced that can have a positive impact to process yield and/or robustness. Here, we show the results of a novel epigenetic inhibitor that improved process yield by approximately two-fold while also having a positive impact to process robustness. An omics approach was then applied to determine the mechanism for this improvement. Rationale media design was then applied to determine the optimal concentration and delivery method for optimizing the fed-batch process. Finally, we explore the molecules impact on product quality and how a robust end-to-end protein platform can mitigate potential product quality comparability risks between development cycles.

Getting more for less: Leveraging epigenetics to increase process yield

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.